As modern societies are gradually aging together with the development of medical technology, age-related diseases with an increasing incidence are emerging as a new social problem. Autoimmune diseases, which are caused by abnormal immunomodulatory activity of immune cells of the human body, such as rheumatic disease or colon diseases, make up a large proportion of the age-related diseases. A method of modulating immune responses through immune cells, such as T cells or macrophagocytes, is receiving renewed attention as an alternative for the treatment of the autoimmune disease. The T cells play a very important role in the immune responses, and the immune responses can be modulated due to the cytokine secretion of T cells. Therefore, the above diseases can be treated by delivering siRNA gene or immune response modulating proteins to modulate immune responses. A T cell-specific carrier is used to deliver the siRNA gene or immune response modulating proteins to T cells, thereby modulating the immune responses of T cells and treating the above diseases.
Recently, studies about the use of antibodies are being conducted in order to deliver cell-specific therapeutic proteins or genes, and here, the specific binding of epitopes of the antibody to antigens is employed. Antibodies produced from rabbits, goats, and rodents are used, but since animal testing is performed on rodents in most study stages, rodent-derived antibodies are used more frequently. As a result of these studies, a muscFvCD7-9R carrier in which Oligo-9-Arginine (9R) binds to mouse-derived scFv (muscFvCD7) specifically binding to CD7, which is the T-cell surface protein, was manufactured. It was verified that, small interfering RNA (siRNA) capable of preventing the infection and replication of AIDS viruses is allowed to bind to the scFvCD7-9R carrier, thereby delivering anti-virus siRNA specifically to T cells, and suppressing replication of viruses, which are previously present in vivo, including the infection and replication of AIDS viruses (Kumar et al., Cell, 2008 Aug. 22; 134(4):577-586).
Nevertheless, CD7-specific scFv (muscFvCD7) used in conventional studies by Kumar et al. (2008) is derived from a rodent (Mus musculus), and exhibits antigenicity in vivo when applied to the humanized mouse or the human body. The carrier having antigenicity as above may cause an immune response in vivo prior to cell-specific delivery of siRNA gene or immune response modulating protein, lowering efficiency of delivering siRNA gene or immune response modulating protein into T cells. Therefore, a humanized single chain antibody for using the foregoing rodent-derived scFv as a carrier needs to be developed.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosures of cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and details of the present invention are explained more clearly.